Single Gene Responsible for Group of Heart Disease Risk Factors

It’s rare, but a genetic mutation may explain the collection of heart-harming factors, including obesity, known as metabolic syndrome

Researchers have been pretty successful at identifying individual genes that can contribute to obesity, diabetes, high blood pressure or high cholesterol levels. Having any—or a combination of these risk factors—can significantly increase the risk of heart disease and stroke.

But by studying three families whose members had higher than average rates of heart disease, diabetes and obesity, researchers zeroed in on a single gene, DYRK1B, that when mutated, can contribute to nearly all of these risk factors, which together are known as metabolic syndrome.

“Historically, there has been debate about the existence of metabolic syndrome. The question is, are the [risk factors] together coincidentally or are they here because the patient has a unifying [problem that explains them all],” says Dr. Ali Keramati, a resident in internal medicine at the Yale University School of Medicine. “This study shows that it’s possible for one patient to have all the risk factors that are all explained by one mutation.”

Normally, that gene is responsible for taking stem cells and turning them into fat or muscle, and for directing the liver to produce glucose to balance out insulin levels. In the aberrant form found among members of the three families, it became overactive, pushing the body to produce more fat cells, and driving the liver to pump out more glucose, raising blood sugar levels. The result is likely metabolic syndrome; family members with the mutated gene were more likely to be obese, have diabetes and early heart disease compared to those who did not.

For those who might think that their genes are to blame for their obesity, hypertension or diabetes, Keramati stresses that the mutation is rare, and likely only explains metabolic syndrome in a very small percentage of people. But for people who are affected, the good news is that a drug may help to control the hyperactivity of the gene. “It may be possible to develop a drug that knocks down the function of this gene,” he says.

And for the vast majority who don’t have the DYRK1B mutation, the finding may still lead to other drug treatments by improving doctors’ understanding of how various risk factors form the perfect storm of conditions for heart. In the meantime, the strongest ways to avoid metabolic syndrome are the most familiar – keeping weight, blood pressure, blood sugar and cholesterol levels under control with a healthy diet and plenty of exercise.